Neophobia, sensory experience and child's schemata contribute to food choices.

PURPOSE: The aim of the present review is to analyze dynamic interactions between nutrigenomics, environmental cues, and parental influence, which can all lead to children's neophobic reactions and its persistence in time. METHODS: We reviewed studies available on electronic databases, conducted on children aged from birth to 18 years. We also considered official websites of Italian Institutions, providing advice on healthy eating during infancy. RESULTS: Modern day societies are faced with an eating paradox, which has severe and ever-growing implications for health. In face of a wider availability of healthy foods, individuals instead often choose processed foods high in fat, salt and sugar content. Economic reasons surely influence consumers' access to foods. However, there is mounting evidence that food choices depend on the interplay between social learning and genetic predispositions (e.g., individual eating traits and food schemata). Neophobia, the behavioral avoidance of new foods, represents an interesting trait, which can significantly influence children's food refusal. Early sensory experiences and negative cognitive schemata, in the context of primary caregiver-child interactions, importantly contribute to the priming of children's food rejection. CONCLUSIONS: As neophobia strongly affects consumption of healthy foods, it will be relevant to rule definitively out its role in the genesis of maladaptive food choices and weight status in longitudinal studies tracking to adulthood and, in meanwhile, implement early in life effective social learning strategies, to reduce long-term effects of neophobia on dietary patterns and weight status. LEVEL OF EVIDENCE: Level II, controlled trials without randomization.

Transcranial Direct Current Stimulation in neurogenetic syndromes: new treatment perspectives for Down syndrome?

This perspective review aims to explore the potential neurobiological mechanisms involved in the application of transcranial Direct Current Stimulation (tDCS) for Down syndrome (DS), the leading cause of genetically-based intellectual disability. The neural mechanisms underlying tDCS interventions in genetic disorders, typically characterized by cognitive deficits, are grounded in the concept of brain plasticity. We initially present the neurobiological and functional effects elicited by tDCS applications in enhancing neuroplasticity and in regulating the excitatory/inhibitory balance, both associated with cognitive improvement in the general population. The review begins with evidence on tDCS applications in five neurogenetic disorders, including Rett, Prader-Willi, Phelan-McDermid, and Neurofibromatosis 1 syndromes, as well as DS. Available evidence supports tDCS as a potential intervention tool and underscores the importance of advancing neurobiological research into the mechanisms of tDCS action in these conditions. We then discuss the potential of tDCS as a promising non-invasive strategy to mitigate deficits in plasticity and promote fine-tuning of the excitatory/inhibitory balance in DS, exploring implications for cognitive treatment perspectives in this population.

Effects of online tDCS and hf-tRNS on reading performance in children and adolescents with developmental dyslexia: a study protocol for a cross sectional, within-subject, randomized, double-blind, and sham-controlled trial.

Background: Developmental Dyslexia (DD) is a brain-based developmental disorder causing severe reading difficulties. The extensive data on the neurobiology of DD have increased interest in brain-directed approaches, such as transcranial direct current stimulation (tDCS), which have been proposed for DD. While positive outcomes have been observed, results remain heterogeneous. Various methodological approaches have been employed to address this issue. However, no studies have compared the effects of different transcranial electrical stimulation techniques (e.g., tDCS and transcranial random noise stimulation, tRNS), on reading in children and adolescents with DD. Methods: The present within-subject, double-blind, and sham-controlled trial aims to investigate the effects of tDCS and hf-tRNS on reading in children and adolescents with DD. Participants will undergo three conditions with a one-week interval session: (A) single active tDCS session; (B) single active hf-tRNS session; and (C) single sham session (tDCS/hf-tRNS). Left anodal/right cathodal tDCS and bilateral tRNS will be applied over the temporo-parietal regions for 20 min each. Reading measures will be collected before and during each session. Safety and blinding parameters will be recordered. Discussion: We hypothesize that tRNS will demonstrate comparable effectiveness to tDCS in improving reading compared to sham conditions. Additionally, we anticipate that hf-tRNS will exhibit a similar safety profile to tDCS. This study will contribute novel insights into the effectiveness of hf-tRNS, expediting the validation of brain-based treatments for DD.

Psychiatric Hospitalization for Psychopathological Disorders and Self-Injurious Behaviors in Italian Children and Adolescents during COVID-19.

The evidence shows that the COVID-19 pandemic dramatically increased the number of urgent psychiatric consultations for children and adolescents in hospital emergency departments (EDs). However, what needs to be further investigated are the characteristics of psychiatric hospitalization in children and adolescents admitted to the Child and Adolescent Neuropsychiatry Unit wards in EDs. Specifically, this retrospective study aimed to examine changes in (i) the number of inpatients and (ii) the distribution of psychopathological disorders and self-injurious behaviors in our Child and Adolescent Neuropsychiatry Unit ward during the COVID-19 lockdown in Italy (March-June 2020; October 2020-January 2021) compared with the same months of previous years. We found a significantly lower number of inpatients during the first four quarantine months than the first four reference months and a higher number of inpatients during the second four quarantine months than the second four reference months. Additionally, we found an increased frequency of mood disorders, non-suicidal self-injurious behavior, and suicidal ideation during the COVID-19 lockdown compared to the reference periods. Our findings underline the need to develop psychological healthcare services for future emergency periods in order to identify and treat psychological distress in children and adolescents early, reducing the risk of psychiatric hospitalization.

The efficacy of non-invasive brain stimulation in the treatment of children and adolescents with Anorexia Nervosa: study protocol of a randomized, double blind, placebo-controlled trial.

BACKGROUND: Current psychological and pharmacological treatments for Anorexia Nervosa (AN) provide only moderate effective support, and there is an urgent need for research to improve therapies, especially in developing age. Non-invasive brain stimulation has suggested to have the potential to reducing AN symptomatology, via targeting brain alterations, such as hyperactivity of right prefrontal cortex (PFC). We suppose that transcranial direct current stimulation (tDCS) to the PFC may be effective in children and adolescents with AN. METHODS: We will conduct a randomized, double blind, add-on, placebo-controlled trial to investigate the efficacy of tDCS treatment on clinical improvement. We will also investigate brain mechanisms and biomarkers changes acting in AN after tDCS treatment. Eighty children or adolescent with AN (age range 10-18 years) will undergo treatment-as-usual including psychiatric, nutritional and psychological support, plus tDCS treatment (active or sham) to PFC (F3 anode/F4 cathode), for six weeks, delivered three times a week. Psychological, neurophysiological and physiological measures will be collected at baseline and at the end of treatment. Participants will be followed-up one, three, six months and one year after the end of treatment. Psychological measures will include parent- and self-report questionnaires on AN symptomatology and other psychopathological symptoms. Neurophysiological measures will include transcranial magnetic stimulation (TMS) with electroencephalography and paired pulse TMS and repetitive TMS to investigate changes in PFC connectivity, reactivity and plasticity after treatment. Physiological measures will include changes in the functioning of the endogenous stress response system, body mass index (BMI) and nutritional state. DISCUSSION: We expect that tDCS treatment to improve clinical outcome by reducing the symptoms of AN assessed as changes in Eating Disorder Risk composite score of the Eating Disorder Inventory-3. We also expect that at baseline there will be differences between the right and left hemisphere in some electrophysiological measures and that such differences will be reduced after tDCS treatment. Finally, we expect a reduction of endogenous stress response and an improvement in BMI and nutritional status after tDCS treatment. This project would provide scientific foundation for new treatment perspectives in AN in developmental age, as well as insight into brain mechanisms acting in AN and its recovery. Trial registration The study was registered at ClinicalTrials.gov (ID: NCT05674266) and ethical approval for the study was granted by the local research ethics committee (process number 763_OPBG_2014).

Methylphenidate is more effective to improve inhibitory control and working memory compared to tDCS in children and adolescents with attention deficit/hyperactivity disorder: a proof-of-concept study.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is characterized by an inappropriate, pervasive and persistent pattern of inattention, hyperactivity, and/or impulsivity and associated with substantial functional impairment. Despite considerable advances in the understanding and management of ADHD, some patients do not respond well to methylphenidate (MPH), the first-choice pharmacological treatment. Over the past decades, among non-invasive brain stimulation techniques, transcranial direct current stimulation (tDCS) has proven to be an effective and safe technique to improve behavior and cognition in children with neurodevelopmental disorders, including ADHD, by modifying cortical excitability. However, the effect of tDCS has never been directly compared with that of the MPH. The present randomized sham-controlled trial evaluated the effect of a single session of anodal tDCS compared with the administration of a single dose of MPH in children and adolescents with ADHD. Methods: After completing baseline assessment (T0), 26 children and adolescents with ADHD were exposed to 3 conditions with a 24-h interval-sessions: (A) a single session of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC); (B) a single session of sham tDCS over the left DLPFC; (C) a single dose of MPH. Results: Our results showed that after administering a single dose of MPH, children and adolescents with ADHD improved inhibitory control and visual-spatial WM compared with baseline, anodal, and sham tDCS. However, a single session of active tDCS over the left DLPFC was not effective compared with either baseline or sham tDCS. Discussion: In conclusion, our protocol in ADHD involving a single tDCS session did not demonstrate consistent improvements in neurocognitive features compared with baseline, sham tDCS, or single MPH administration. Different protocols need to be developed to further test the effectiveness of tDCS in improving ADHD symptoms.

Anxiety, concerns and COVID-19: Cross-country perspectives from families and individuals with neurodevelopmental conditions.

Background: The COVID-19 pandemic had a major impact on the mental health and well-being of children with neurodevelopmental conditions (NDCs) and of their families worldwide. However, there is insufficient evidence to understand how different factors (e.g., individual, family, country, children) have impacted on anxiety levels of families and their children with NDCs developed over time. Methods: We used data from a global survey assessing the experience of 8043 families and their children with NDCs (mean of age (m) = 13.18 years, 37% female) and their typically developing siblings (m = 12.9 years, 45% female) in combination with data from the European Centre for Disease Prevention and Control, the University of Oxford, and the Central Intelligence Agency (CIA) World Factbook, to create a multilevel data set. Using stepwise multilevel modelling, we generated child-, family- and country-related factors that may have contributed to the anxiety levels of children with NDCs, their siblings if they had any, and their parents. All data were reported by parents. Results: Our results suggest that parental anxiety was best explained by family-related factors such as concerns about COVID-19 and illness. Children's anxiety was best explained by child-related factors such as children's concerns about loss of routine, family conflict, and safety in general, as well as concerns about COVID-19. In addition, anxiety levels were linked to the presence of pre-existing anxiety conditions for both children with NDCs and their parents. Conclusions: The present study shows that across the globe there was a raise in anxiety levels for both parents and their children with NDCs because of COVID-19 and that country-level factors had little or no impact on explaining differences in this increase, once family and child factors were considered. Our findings also highlight that certain groups of children with NDCs were at higher risk for anxiety than others and had specific concerns. Together, these results show that anxiety of families and their children with NDCs during the COVID-19 pandemic were predicted by very specific concerns and worries which inform the development of future toolkits and policy. Future studies should investigate how country factors can play a protective role during future crises.

Age-related clinical characteristics of children and adolescents with ADHD.

Introduction: Attention deficit hyperactivity disorder (ADHD) has been associated with difficulties in regulating aversion states, high functional impairment, and a high risk of psychopathology across the lifespan. ADHD is clinically heterogeneous, with a wide spectrum of severity and associated symptoms. Clinical characteristics need to be carefully defined in different periods of life as ADHD course, symptoms, and comorbidities may fluctuate and change over time. Adolescence usually represents the transition from primary to secondary education, with a qualitative and quantitative change in environmental and functional demands, thus driving symptoms' change. Methods: In order to characterize age-related clinical features of children (<11 years) and adolescents (≥11 years) with ADHD, we conducted a naturalistic study on 750 children and adolescents assessed for ADHD at our Neuropsychiatry Unit over the course of 3 years (2018-2020). Results: We found that ADHD symptoms were significantly higher in children than adolescents. More importantly, we found worse global functioning, lower adaptive skills, higher levels of anxiety and depressive symptoms, somatic complaints, emotional dysregulation, social problems, and aggression in adolescents, despite a lower severity of ADHD-specific symptoms. Conclusion: These results should be confirmed in longitudinal observational studies of adequate sample size in order to reliably describe a potential course characterized by worsening of functioning, reduction in ADHD-specific symptoms and increase in general psychopathology during the transition from childhood to adolescence.

Psychiatric Comorbidities in Children and Adolescents with High-Functioning Autism Spectrum Disorder: A Study on Prevalence, Distribution and Clinical Features in an Italian Sample.

This study investigated the prevalence and distribution of psychiatric comorbidities in a group of 472 children and adolescents with ASD aged 3-18 years. We examined differences in age, sex, IQ, adaptive skills, and ASD symptom severity by comparing participants with ASD (ASD group) with participants with ASD and a psychiatric disorder (ASD/PSY group). Overall, 32.2% of participants had a comorbid psychiatric condition. Attention deficit/hyperactivity disorder (ADHD) was the most frequent diagnosis among preschoolers (20.4%); among school-age children, ADHD and anxiety/obsessive-compulsive disorders were the most frequent conditions (21% and 10.6%, respectively); finally, adolescents exhibit higher prevalence of anxiety/obsessive-compulsive disorders (21.8%). The ASD/PSY group showed a higher percentage of males, they were older and showed lower adaptive skills than the group with ASD; moreover, their mothers exhibited higher stress levels than mothers of participants in the ASD group. The comparison between age groups in participants within ASD/PSY group revealed that preschoolers had lower IQ than school-age children and adolescents, and worse adaptive skills, more repetitive behaviors, and restricted interests than adolescents. This study highlights the importance of an accurate diagnosis of psychiatric comorbidities in children and adolescents with ASD, also considering individual and family impairment.

Sensory Processing Disorders in Children and Adolescents: Taking Stock of Assessment and Novel Therapeutic Tools.

Sensory processing disorders (SPDs) can be described as difficulty detecting, modulating, interpreting, and/or responding to sensory experiences. Because SPDs occur in many individuals with autism spectrum disorder and in other populations with neurodevelopmental disorders, it is important to distinguish between typical and atypical functioning in sensory processes and to identify early phenotypic markers for developing SPDs. This review considers different methods for diagnosing SPDs to outline a multidisciplinary approach useful for developing valid diagnostic measures. In particular, the advantages and limitations of the most commonly used tools in assessment of SPDs, such as caregiver reports, clinical observation, and psychophysical and neuroimaging studies, will be reviewed. Innovative treatment methods such as neuromodulation techniques and virtual reality will also be suggested.

Distance learning during COVID-19 lockdown: Impact on adolescents with specific learning disorders and their parents.

Background: The transition of teaching from in-person to Distance Learning (DL) due to the COVID-19 pandemic led to negative effects on students' psychological wellbeing and academic achievement. The worst consequences have been experienced by students with so-called special educational needs, as well as by their parents. However, very little emphasis has been placed on the effects of DL in students with Specific Learning Disorders (SLD). The present work aimed to evaluate the effects of DL during the COVID-19 lockdown in Italian students with SLD and in their parents. Methods: An online survey was administered to 92 students with SLD and their parents after the COVID-19 lockdown. The survey consisted of four sections: participants' demographic information; perceived stress related to general aspects (i.e., social and family determinants) as well as specific aspects related to DL; attitudes and feelings toward DL; and academic grades before and after DL. Results: Students with SLD perceived stress mainly from social isolation/distancing and DL (p always ≤ 0.0001), especially from online classes and oral exams (p always ≤ 0.0001). Students who did not benefit from appropriate accommodations (i.e., individualized teaching and learning methods) during DL perceived 3 times more DL-related stress than those who used them as in-person learning (OR = 3.00, CI 95%: 1.24-7.28, p = 0.015). Girls perceived more stress from online lessons (OR = 0.40, CI 95%: 0.16-0.96, p = 0.04) and use of devices (OR = 0.33, CI 95%: 0.14-0.80, p = 0.015) than boys. Negative feelings (less motivation, reduced ability to understand lessons, interact, and stay focused) and positive feelings (less anxiety and more self-confidence with its own rate of learning) toward DL emerged. Higher academic grades also was observed after DL (p ≤ 0.0001). Lastly, strong and positive correlations emerged between students' and parents' perceived stress during DL (p always < 0.001). Implications: The present study prompts special considerations for students with special educational needs not only when providing conventional instruction, but especially when it is necessary to suddenly modify teaching approaches.

Effects of a short and intensive transcranial direct current stimulation treatment in children and adolescents with developmental dyslexia: A crossover clinical trial.

Developmental Dyslexia (DD) significantly interferes with children's academic, personal, social, and emotional functioning. Nevertheless, therapeutic options need to be further validated and tested in randomized controlled clinical trials. The use of transcranial direct current stimulation (tDCS) has been gaining ground in recent years as a new intervention option for DD. However, there are still open questions regarding the most suitable tDCS protocol for young people with DD. The current crossover study tested the effectiveness of a short and intensive tDCS protocol, including the long-term effects, as well as the influence of age and neuropsychological processes at baseline on reading improvements. Twenty-four children and adolescents with DD were randomly assigned to receive active tDCS during the first slot and sham tDCS during the second slot or vice versa. Five consecutive daily sessions of left anodal/right cathodal tDCS set at 1 mA for 20 min were administered over the parieto-occipital regions. Reading measures (text, high frequency word, low frequency word, and non-word lists) and neuropsychological measures (visual-spatial and verbal working memory, phoneme blending, and rapid automatized naming tasks) were collected before, immediately after, 1 week and 1 month later the treatment. Our results showed that only the active tDCS condition improved non-word reading speed immediately after and 1 month later the end of the treatment compared with baseline. In addition, the improvement in non-word reading speed was significantly correlated with age and with neuropsychological measures (verbal working memory and phoneme blending) at baseline but only in the active tDCS condition. The current crossover study contributed to enforce previous effects of tDCS, including long-term effects, on non-word reading speed and to understand the effect of age and neuropsychological processes on reading outcomes. Our findings showed that tDCS could be a low-cost and easy-to-implement treatment option with long-term effects for children and adolescents with DD.

The Strengths and Difficulties Questionnaire as a Valuable Screening Tool for Identifying Core Symptoms and Behavioural and Emotional Problems in Children with Neuropsychiatric Disorders.

The Strengths and Difficulties Questionnaire (SDQ) is a worldwide questionnaire used for the early identification of behavioural/emotional symptoms in children and adolescents with neuropsychiatric disorders. Although its prognostic power has been studied, it has not yet been tested whether SDQ: (i) can identify pathognomonic symptoms across a variety of neurodevelopmental and neuropsychiatric disorders, (ii) can capture emotional and behavioural problems associated with the main diagnosis, as well as shared transdiagnostic dimensions, and (iii) can detect changes in symptomatology with age. The present study evaluated nearly 1000 children and adolescents overall with Global Developmental Delay (GDD), Intellectual Disability (ID), Language Disorder (LD), Specific Learning Disorder (SLD), Autism Spectrum Disorder (ASD), Attention Deficit/Hyperactivity Disorder (ADHD), Mood Disorder (MD), Anxiety Disorder (AD), and Eating Disorders (ED). We found that SDQ: (i) can identify the core symptoms in children with ASD, ADHD, MD, and AD via specific subscales; (ii) can capture the associated emotional and behavioural symptoms in children with LD, GDD, ID, SLD, and ED; and (iii) can detect changes in the symptomatology, especially for GDD, LD, ASD, ADHD, and AD. SDQ is also able to recognise the transdiagnostic dimensions across disorders. Our results underscore the potential of SDQ to specifically differentiate and identify behavioural/emotional profiles associated with clinical diagnosis.

Sleep Disturbances in Children with Attentional Deficit Hyperactivity Disorder and Specific Learning Disorders.

Sleep disturbances may be a significant source of distress for children with neurodevelopmental disorders, and consequently also for their families. Crucially, sleep disturbances might be influenced by comorbidity. Attention deficit hyperactivity disorder (ADHD) and specific learning disorder (SLD) often co-occur, and consequently, investigating sleep disturbances in children with comorbidity of ADHD and SLD is essential. Our study aimed at detecting sleep difficulties in a group of 74 children with ADHD, 78 children with SLD, and 76 children with ADHD and SLD by using the Sleep Disturbances Scale for Children. The results showed that sleep difficulties emerge more clearly in children with comorbid ADHD and SLD compared to children with only ADHD or SLD. These sleep difficulties were not due to differences in ages and behavioral/emotional problems. In conclusion, evaluating sleep disturbances is important when assessing and managing children with ADHD, SLD, and particularly with the two comorbid conditions, to better understand their difficulties and develop tailored interventions.

Comparing the Effect of Methylphenidate and Anodal tDCS on Inhibitory Control and Working-Memory in Children and Adolescents with Attention Deficit/Hyperactivity Disorder: A Study Protocol for a Randomized, within-Subject Trial.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inappropriate levels of attention, hyperactivity, and impulsivity that interfere with individual functioning. The international guidelines recommend targeting ADHD-related neurochemical brain abnormalities by intervening via drug treatment, such as methylphenidate (MPH), as first choice. Drug treatments are usually associated with a huge amount of cost for families and the healthcare system, suspension for low compliance, poor long-term efficacy, and side effects. Transcranial direct current stimulation (tDCS) has been suggested as a possible noninvasive means to safely manipulate brain activity and, in turn, improve behavior and cognition in developmental ages. Several studies have shown that tDCS has the potential to improve ADHD-related cognitive deficits, but the effect of tDCS compared with MPH has never been evaluated. The aim of the present within-subject, sham-controlled, randomized proof-of-concept study is to demonstrate the positive effect of one-session anodal tDCS analogous to the MPH drug on inhibitory control and working memory in children and adolescents with ADHD. We strongly believe that this study protocol will serve to accelerate research into low-cost, drug-free, feasible interventions for ADHD.

Understanding the Effects of Transcranial Electrical Stimulation in Numerical Cognition: A Systematic Review for Clinical Translation.

Atypical development of numerical cognition (dyscalculia) may increase the onset of neuropsychiatric symptoms, especially when untreated, and it may have long-term detrimental social consequences. However, evidence-based treatments are still lacking. Despite plenty of studies investigating the effects of transcranial electrical stimulation (tES) on numerical cognition, a systematized synthesis of results is still lacking. In the present systematic review (PROSPERO ID: CRD42021271139), we found that the majority of reports (20 out of 26) showed the effectiveness of tES in improving both number (80%) and arithmetic (76%) processing. In particular, anodal tDCS (regardless of lateralization) over parietal regions, bilateral tDCS (regardless of polarity/lateralization) over frontal regions, and tRNS (regardless of brain regions) strongly enhance number processing. While bilateral tDCS and tRNS over parietal and frontal regions and left anodal tDCS over frontal regions consistently improve arithmetic skills. In addition, tACS seems to be more effective than tDCS at ameliorating arithmetic learning. Despite the variability of methods and paucity of clinical studies, tES seems to be a promising brain-based treatment to enhance numerical cognition. Recommendations for clinical translation, future directions, and limitations are outlined.

Moderators and Other Predictors of Methylphenidate Response in Children and Adolescents with ADHD.

Methylphenidate (MPH) is the treatment of first choice for developmental ADHD. To date, no reliable method to predict how patients will respond to MPH exists and conflicting results are reported on clinical characteristics of responders. The present study aims to give a more precise characterization of the patients who will respond best to MPH to help clinicians in defining the treatment plan. Age, neuropsychological functioning (i.e., attention and working memory), and behavioral/emotional symptoms of 48 drug-naïve children and adolescents with ADHD (42 boys and 6 girls, age-range 6-16 years, mean age 10.5 ± 2.5 years, mean IQ 101.3 ± 11.2) were studied to assess how these different characteristics affected a single-dose MPH response. Four hierarchical linear regression models were used to explore whether age, neuropsychological measures at baseline, and behavioral/emotional symptoms could predict attention and working memory measures after a single-dose MPH administration. We found that improvement in attention and working memory was predicted by age, neuropsychological measures at baseline, and severity of ADHD symptoms. No behavioral and emotional symptoms predicted single-dose MPH response with the exception of conduct symptoms.

Cerebellar Agenesis and Bilateral Polimicrogyria Associated with Rare Variants of CUB and Sushi Multiple Domains 1 Gene (CSMD1): A Longitudinal Neuropsychological and Neuroradiological Case Study.

Cerebellar agenesis is an extremely rare condition characterized by a near complete absence of the cerebellum. The pathogenesis and molecular basis remain mostly unknown. We report the neuroradiological, molecular, neuropsychological and behavioral characterization of a 5-year-old girl, with cerebellar agenesis associated with parietal and peri-Sylvian polymicrogyria, followed-up for 10 years at four time points. Whole exome sequencing identified two rare variants in CSMD1, a gene associated with neurocognitive and psychiatric alterations. Mild intellectual impairment, cerebellar ataxia and deficits in language, memory and executive functions, with relatively preserved adaptive and psychopathological domains, were initially showed. Phonological awareness and verbal memory declined at 11 years of age, and social and anxiety problems emerged. Adaptive and psychopathological characteristics dramatically worsened at 15 years. In summary, the developmental clinical outcome showed impairment in multiple cognitive functions in childhood, with a progressive decline in cognitive and adaptive abilities and the emergence of psychopathological symptoms in adolescence. The observed phenotype could be the result of a complex interplay between cerebellar abnormality, brain malformation and the relations with CSMD1 variants. These findings may provide insights into the developmental clinical outcomes of a co-occurrence between rare brain malformation and rare genetic variants associated to neurodevelopmental disorders.

Clinical characteristics of children and adolescents with ADHD with or without methylphenidate prescription at their first diagnostic assessment.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most prevalent neurodevelopmental disorder diagnosed in the scholar age. It is associated with significant impairment in global functioning, and in moderate/severe presentations the outcome is critically dependent on pharmacological optimization of the multi-modal treatment. Methylphenidate (MPH) is the first-choice pharmacological treatment in children and adolescents with ADHD, with substantial evidence of significant efficacy and effectiveness on global functioning and symptoms' severity. There is some evidence supporting a few clinical and socio-demographic variables as predictors of pharmacological treatment prescription in children with ADHD independently of ADHD symptoms severity. However, it is warranted to investigate clinical and general psychopathological characteristics potentially associated with negative outcomes and the need for pharmacological treatment to inform appropriate prescription strategies. In this context, we compared 268 children and adolescents who were prescribed MPH (ADHD/MPH) for the first time after their first diagnostic assessment at our center, and 444 children and adolescents with ADHD (ADHD/noMPH) who were recommended non-pharmacological evidence-based interventions alone. ADHD/MPH group had higher severity of non-ADHD psychopathological symptoms compared to the ADHD/noMPH group, as documented by higher scores on the Child Behavior Checklist (CBCL) subscales, higher severity of ADHD symptoms, lower average IQ and lower adaptive levels independently of IQ. More specifically, beside externalizing symptoms, also internalizing symptoms were significantly higher in the ADHD/MPH group. The presence of significant non-ADHD psychopathology should be considered as a clinical factor associated with the need for MPH prescription in children and adolescents with ADHD.